The human placental growth hormone variant is mitogenic for rat lymphoma Nb2 cells.
Although there is evidence that human (h) placental GH variant (hGH-V) possesses a growth-promoting function, lactogenic activity by the hormone has not been demonstrated. Rat anterior pituitary tumor (GC) cells stably transfected with the hGH-V gene (GC [hGH-V] cells) synthesize and secrete hGH-V. This hormone shares considerable structural similarity with pituitary growth hormone (hGH-N) and chorionic somatomammotropin (hCS) at the nucleotide (greater than 90%) and amino acid (greater than 80%) levels. As expected, both hGH-N and hCS antibodies detect hGH-V by immunoblotting. However, hGH-V, but not hGH-N or hCS, cross-reacts with human or rat pituitary prolactin (PRL) antibodies. These data indicate that structural features shared by hGH-V and pituitary PRL are not present in hGH-N or hCS. Comparison of amino acid sequences implicates two regions that may account for a common epitope between hGH-V and hPRL, and structural difference from hGH-N and hCS. The possible lactogenic activity by hGH-V was assessed in a rat lymphoma Nb2 cell bioassay. Conditioned medium from GC[hGH-V] cells permitted growth of lactogen-dependent Nb2 lymphoma cells in culture. This activity was blocked by antibodies raised to rat PRL but not hPRL or hGH-N. Comparison of the hGH-V amino acid sequence with those from 14 other lactogenic hormones, including hPRL, hCS and hGH-N, reveals 6 conserved amino acids. These data indicate a lactogenic as well as growth-promoting function for the secreted hGH-V protein in vivo.
Nickel
B E
BE
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Kardami
E
E
Cattini
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D014644:Genetic Variation; D013006:Growth Hormone / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D008223:Lymphoma / Q000473:pathology*; D008969:Molecular Sequence Data; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D010920:Placenta / Q000032:analysis*; D011388:Prolactin / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D011388:Prolactin; D013006:Growth Hormone